The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Criteria Specification: CSpec Registry PDF

Variant: NM_000277.2(PAH):c.355C>T (p.Pro119Ser)

CA220582

92741 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 38a183ee-7e53-4c24-a250-50958f390c78

HGVS expressions

NM_000277.2:c.355C>T
NM_000277.2(PAH):c.355C>T (p.Pro119Ser)
NC_000012.12:g.102877548G>A
CM000674.2:g.102877548G>A
NC_000012.11:g.103271326G>A
CM000674.1:g.103271326G>A
NC_000012.10:g.101795456G>A
NG_008690.1:g.45055C>T
NG_008690.2:g.85863C>T
NM_000277.1:c.355C>T
NM_001354304.1:c.355C>T
NM_000277.3:c.355C>T
ENST00000307000.7:c.340C>T
ENST00000549111.5:n.451C>T
ENST00000550978.6:n.339C>T
ENST00000551337.5:c.355C>T
ENST00000551988.5:n.444C>T
ENST00000553106.5:c.355C>T

Likely Pathogenic

Met criteria codes 3
PP3 PM3_Strong PP4_Moderate
Not Met criteria codes 1
PM2

Expert Panel

Evidence Links 2

Evidence submitted by expert panel
PAH VCEP
PAH-specific ACMG/AMP criteria applied: PP3: in silico analysis supportive of damaging effect; PM3_Strong: In trans with R261Q (PMID 21147011), and in trans with IVS2+1G>A (PMID 12655554) (PMID:21147011; PMID:12655554); PP4_Moderate: BH4 deficiency excluded (PMID:21147011). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PP3, PM3_Strong, PP4_Moderate).
Met criteria codes
PP3
in silico analysis supportive of damaging effect
PM3_Strong
In trans with R261Q (PMID 21147011), and in trans with IVS2+1G>A (PMID 12655554)

PP4_Moderate
BH4 deficiency excluded

Not Met criteria codes
PM2
PAH specific specifications state PM2 criteria as 0.02% (AF=0.0002)
Approved on: 2018-07-29
Published on: 2019-04-06
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